ZIP Code to Genomic Code: Neighborhood Disadvantage, Aggressive Breast Cancer Biology, and Breast Cancer Outcomes.

OBJECTIVE: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. BACKGROUND: ND is associated with shorter breast cancer recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. METHODS: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on the protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity [nuclear factor-κB ( NF-kB ), activator protein 1 ( AP-1 )], sympathetic nervous system (SNS) activity [cyclic 3'-5' adenosine monophosphate response element-binding protein ( CREB )], and protective cellular responses [interferon-regulatory factor ( IRF ) and signal transducer and activator of transcription ( STAT )]. To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. RESULTS: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB , activator protein 1, down-regulated IRF , and signal transducer and activator of transcription) and SNS activation (up-regulated CREB ). Increasing subjective ND (eg, threat to safety) was associated with up-regulated NF-kB and CREB and down-regulated IRF . These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. CONCLUSIONS: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

Does structural racism impact receipt of NCCN guideline-concordant breast cancer treatment?

PURPOSE: Disparities in breast cancer survival remain a challenge. We aimed to analyze the effect of structural racism, as measured by the Index of Concentration at the Extremes (ICE), on receipt of National Cancer Center Network (NCCN) guideline-concordant breast cancer treatment. METHODS: We identified patients treated at two institutions from 2005 to 2017 with stage I-IV breast cancer. Census tracts served as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed to create 5 models, controlling for economic segregation, non-Hispanic Black (NHB) segregation, NHB/economic segregation, Hispanic segregation, and Hispanic/economic segregation. Multi-level logistic regression models were used to determine the association between individual and neighborhood-level characteristics on receipt of NCCN guideline-concordant breast cancer treatment. RESULTS: 5173 patients were included: 55.2% were Hispanic, 27.5% were NHW, and 17.3% were NHB. Regardless of economic or residential segregation, a NHB patient was less likely to receive appropriate treatment [(OR)Model1 0.58 (0.45-0.74); ORModel2 0.59 (0.46-0.78); ORModel3 0.62 (0.47-0.81); ORModel4 0.53 (0.40-0.69); ORModel5 0.59(0.46-0.76); p < 0.05]. CONCLUSION: To our knowledge, this is the first analysis assessing receipt of NCCN guideline-concordant treatment by ICE, a validated measure for structural racism. While much literature emphasizes neighborhood-level barriers to treatment, our results demonstrate that compared to NHW patients, NHB patients are less likely to receive NCCN guideline-concordant breast cancer treatment, independent of economic or residential segregation. Our study suggests that there are potential unaccounted individual or neighborhood barriers to receipt of appropriate care that go beyond economic or residential segregation.

Associations Between Neighborhood-Level Income and Triple-Negative Breast Cancer in a Majority-Minority Population.

BACKGROUND: Previous studies on disparities in triple-negative breast cancer (TNBC) focus on race/ethnicity, with few exploring the impact of contextual factors such as neighborhood-level income. This study evaluates the effect of neighborhood-level income on disparities in TNBC among a racially and ethnically diverse cohort, after accounting for granular individual-level risk factors of TNBC. PATIENTS AND METHODS: Patients with stage I-IV breast cancer from 2005 to 2017 were identified from our local tumor registry. The primary outcome was diagnosis of TNBC. Using 5-years estimates from the American Community Survey, we obtained median household income for each census tract which was categorized into quartiles. Mixed effects logistic regression was conducted and stratified by race and ethnicity, controlling for individual-level sociodemographic, comorbidities, and tumor characteristics. RESULTS: Among 5377 breast cancer registry patients, 16.5% were diagnosed with TNBC. The majority were Hispanic (50.1%) followed by non-Hispanic Black (NHB) (28.0%). After controlling for individual-level covariables including race and ethnicity, comorbidities, and tumor characteristics, women from low-income neighborhoods had increased odds of TNBC compared with other breast cancer subtypes, compared with those in high-income neighborhoods [odds ratio (OR) 1.33; 95% confidence interval (CI) 1.04, 1.70, p < 0.001]. In stratified analyses, NHB patients from low-income neighborhoods had two times the odds of TNBC diagnosis compared with those from high-income neighborhoods (OR 2.11; 95% CI 1.02, 4.37). CONCLUSION: We found that living in a low-income neighborhood is associated with an increased odds of TNBC independent of granular individual-level TNBC risk factors, particularly NHB race. More striking, NHB living in low-income neighborhoods had increased odds of TNBC compared with NHB living in high-income neighborhoods. Our results suggest potential unaccounted gene-environment and/or social (api)genomic interactions between neighborhood-level income and TNBC subtype development.

The Enigma That is Rectal Squamous Cell Carcinoma: A Case Series.

INTRODUCTION: Colorectal cancer is the third most common cancer and the third leading cause of cancer deaths in the United States. As rectal squamous cell carcinoma (SCC) is an uncommon colorectal cancer, there is limited data on this clinical entity. We aimed to evaluate the tumor characteristics, treatment, and clinical outcomes of this rare deadly disease. METHODS: Pathological specimens from 2017 to 2022 at a single National Cancer Institute-designated cancer center were screened for all rectal cases with a diagnosis of SCC. All patients with a primary rectal SCC were included. Patients who had extension to the dentate line or evidence of an anal mass, and those who were treated at an outside institution, were excluded. Demographic, treatment, outcome, and surveillance data was extracted. RESULTS: There were 56 specimens identified, nine of which met inclusion criteria. Most patients were White (78%), Hispanic (78%), and female (67%). The average age at diagnosis was 57 y [52-65]. All patients had nodal involvement at the time of clinical staging. All patients were treated with Nigro protocol, with one patient treated with surgery first. The median time of follow-up was 12 mo after initial treatment, 33% had recurrence, with median time to recurrence of 25 mo. Overall, mortality from rectal SCC was 33% at a median time of 37 mo from initial diagnosis. CONCLUSIONS: Rectal SCC is a colorectal cancer that is not fully understood. Our findings showed that treatment mirrors that of anal SCC, with similar rates of survival to both rectal adenocarcinoma and anal SCC.

Effects of neighborhood disadvantage on cortisol and interviewer-rated anxiety symptoms in breast cancer patients initiating treatment.

PURPOSE: Shorter breast cancer (BC) survival outcomes persist by neighborhood disadvantage independent of patient, tumor, and treatment characteristics. This suggests unaccounted mechanisms by which neighborhood disadvantage "gets under the skin" to impact BC survival outcomes. Here, we evaluate the relationship between neighborhood disadvantage and clinical and neuroendocrine markers of stress in BC patients. METHODS: Women with stage 0-III BC were enrolled 2-10 weeks post-surgery and before initiating adjuvant treatment in a study examining stress and stress management processes. Women provided an afternoon-evening (PM) serum cortisol sample and were administered the Hamilton Anxiety Rating Scale (HAM-A). Home addresses were used to determine the Area Deprivation Index (ADI), a validated measure of neighborhood disadvantage. Multiple regression assessed the relationship between ADI and PM serum cortisol and the presence of elevated HAM-A symptoms. RESULTS: Our sample (n = 225) was predominately middle-aged (M = 50.4 years; range 23-70 years), non-Hispanic White (64.3%), with stage I (38.1%), or II (38.6%) disease. The majority (n = 175) lived in advantaged neighborhoods (ADI 1-3). After controlling for age, stage, and surgery type, women from high ADI (4-10) (vs low ADI) neighborhoods had higher PM cortisol levels (ß = 0.19, 95% CI [0.24, 5.00], p = 0.031) and were nearly two times as likely to report the presence of elevated anxiety symptoms (OR = 1.96, 95% CI [1.00, 3.86], p = 0.050). CONCLUSION: Neighborhood disadvantage is significantly associated with higher levels of PM cortisol and elevated anxiety symptoms suggesting stress pathways could potentially contribute to relationships between neighborhood disadvantage and BC survival.

Readmissions to an alternate hospital in patients undergoing vascular intervention for claudication and critical limb ischemia associated with significantly higher mortality.

BACKGROUND: Hospital readmissions with 30 days after vascular surgical interventions have been associated with increased morbidity, mortality, and cost. Readmission rates, now a Centers for Medicare and Medicaid Services quality measure, have been studied in databases that have excluded certain payer types and states and have not accounted for readmission to a hospital different from that of the index admission. More accurate and nationally representative data are needed, because this fragmentation of care could lead to flawed conclusions. The purpose of the present study was to examine the incidence and risk factors for readmission to a nonindex hospital for patients admitted for claudication or critical limb ischemia (CLI). We also examined how this disruption of patient care affects mortality. METHODS: The 2013 to 2014 Nationwide Readmissions Database was queried for all patients admitted for claudication or CLI who had undergone angioplasty, lower extremity bypass, or aortobifemoral bypass. The outcomes of interest were 30- and 365-day readmission rates to any hospital, 30- and 365-day readmission rates to a nonindex hospital, and mortality rates. Multivariable logistic regression was used to identify risk factors for readmission to a nonindex hospital. The most common readmission diagnoses and diagnosis-related groups were identified. RESULTS: A total of 92,769 patients had been admitted with peripheral vascular disease (33,055 with claudication and 59,714 with CLI). The 30- and 365-day readmission rate was 8.97% and 21.49% and 19.26% and 40.36%, for claudication and CLI, respectively. Of the 30- and 365-day readmissions, 20.47% and 24.92% had occurred at a nonindex hospital, respectively. Significantly higher mortality rates were found for patients with 30- or 365-day readmissions to different hospitals (odds ratio, 1.4 and 1.8, respectively). Multivariable analysis revealed that procedural indication and angioplasty are not significant risk factors for readmission to a different hospital. However, female sex, length of stay >7 days, and Charlson Comorbidity Index >3 remained significant risk factors for nonindex readmissions. The most common disease groups for nonindex readmission were "septicemia and disseminated infections" (6.5%), "heart failure" (6.4%), "other vascular procedures" (6.1%), and "amputation of lower limb except toes" (4.0%). CONCLUSIONS: Previously unreported, ≥1 in 4 readmissions after lower extremity vascular procedures for peripheral vascular disease will occur at a nonindex hospital. This fragmentation of care is associated with increased mortality and has serious implications for guiding outcome and quality measures. With a sizeable portion of patients missed by current metrics, concern exists that providers are using flawed data. Further study into social- and patient-specific risk factors might provide methods to prevent these readmissions and improve outcomes in this difficult patient population.

Neighborhood Disadvantage and Breast Cancer-Specific Survival in the US.

Importance: Despite improvements in breast cancer screening, treatment, and survival, disparate breast cancer-specific survival outcomes persist, particularly in disadvantaged neighborhoods. Most of these disparities are attributed to disparities in individual, tumor, and treatment characteristics. However, a critical knowledge gap exists as to whether disparities in breast cancer-specific survival remain after accounting for individual, tumor, and treatment characteristics. Objective: To evaluate if neighborhood disadvantage is associated with shorter breast cancer-specific survival after controlling for individual, tumor, and treatment characteristics in a national population. Design, Setting, and Participants: This national retrospective cohort study included patients with breast cancer diagnosed from 2013 to 2018 from the Surveillance, Epidemiology, and End Results 17 Census tract-level socioeconomic status and rurality database of the National Cancer Institute. Data analysis was performed from September 2022 to December 2023. Exposures: Neighborhood disadvantage measured by Yost index quintiles. Main Outcomes and Measures: Breast cancer-specific survival was evaluated using a competing risks cause-specific hazard model controlling for age, race, ethnicity, rurality, stage, subtype, insurance, and receipt of treatment. Results: A total of 350 824 patients with breast cancer were included; 41 519 (11.8%) were Hispanic, 39 631 (11.3%) were non-Hispanic Black, and 234 698 (66.9%) were non-Hispanic White. A total of 87 635 patients (25.0%) lived in the most advantaged neighborhoods (group 5) and 52 439 (14.9%) lived in the most disadvantaged neighborhoods (group 1). A larger number of non-Hispanic White patients (66 529 patients [76.2%]) lived in advantaged neighborhoods, while disadvantaged neighborhoods had the highest proportion of non-Hispanic Black (16 141 patients [30.9%]) and Hispanic patients (10 168 patients [19.5%]). Breast cancer-specific survival analysis found the most disadvantaged neighborhoods (group 1) had the highest risk of mortality (hazard ratio, 1.43; 95% CI, 1.36-1.50; P < .001) compared with the most advantaged neighborhoods. Conclusions and Relevance: In this national cohort study of patients with breast cancer, neighborhood disadvantage was independently associated with shorter breast cancer-specific survival even after controlling for individual-level factors, tumor characteristics, and treatment. This suggests potential unaccounted-for mechanisms, including both nonbiologic factors and biologic factors.

Rural Melanoma Patients Have Less Surgery and Higher Melanoma-Specific Mortality.

BACKGROUND: Melanoma causes most skin cancer-related deaths, and disparities in mortality persist. Rural communities, compared to urban, face higher levels of poverty and more barriers to care, leading to higher stage at presentation and shorter survival in melanoma. To further evaluate these disparities, we sought to assess the association between rurality and melanoma cause-specific mortality and receipt of recommended surgery in a national cohort. METHODS: Patients with primary non-ocular, cutaneous melanoma from the SEER database, 2000-2017, were included. Outcomes included melanoma-specific survival and receipt of recommended surgery. Rurality was based on Rural-Urban Continuum Codes. Variables included age, sex, race, ethnicity, income, and stage. Multivariate regression models assessed the effect of rurality on survival and receipt of recommended surgery. RESULTS: 103,606 patients diagnosed with non-ocular cutaneous primary melanoma met criteria during this period. 93.3% (n = 96620) were in urban areas and 6.7% (n = 6986) were in rural areas. On multivariate regression controlling for age, sex, race, ethnicity, and stage patients living in a rural area were less likely to receive recommended surgery (aOR .52, 95% CI: .29-.90, P = .02) and had increased hazard of melanoma-specific mortality (aHR 1.19, 95% CI: 1.02-1.40, P = .03) even after additionally controlling for surgery receipt. CONCLUSION: Using a large national cohort, our study found that rural patients were less likely to receive recommended surgery and had shorter melanoma cause-specific survival. Our findings highlight the importance of access to cancer care in rural areas and how this ultimately effects survival for these patients.

Unmet Social Needs and Breast Cancer Screening Utilization and Stage at Presentation.

Importance: Unmet social needs in local populations may hinder the development of targeted cancer control interventions aimed at improving screening utilization and early-stage breast cancer diagnosis to ultimately improve breast cancer survival disparities. Objective: To evaluate if (1) city-funded screening mammography is associated with utilization of screening mammography, (2) unmet social needs are associated with utilization of screening mammography, and (3) unmet social needs are associated with later-stage disease at diagnosis. Design, Setting, and Participants: This cohort study included patients with stages I-IV invasive ductal or lobular carcinoma treated at an academic medical center (including both an underserved safety-net hospital [SNH] and a National Cancer Institute-designated academic cancer center [ACC]) from 2020 to 2023. Eligible patients were aged 18 years or older and able to consent. Data were analyzed between July 2023 and September 2023. Exposure: The Health Leads Social Needs Screening Toolkit, a screening tool that gathers information on the most common social need domains affecting patient health. Main Outcomes and Measures: Univariable and multivariable logistic regression was utilized to evaluate the following primary outcomes: (1) routine screening mammography and (2) American Joint Committee on Cancer 8th edition clinical stage at presentation. Results: Of the 322 women who completed the Health Leads Social Needs Screening Toolkit, 201 (62%) self-identified as Hispanic, 63 (19%) as non-Hispanic Black, and 63 (19%) as non-Hispanic White. Two hundred fifty-five (76%) patients with access to city-funded screening mammography completed a screening mammogram. Patients who presented to the SNH were more likely to present with late-stage disease compared with early-stage disease (15 of 48 [31%] vs 50 of 274 [18%]; P = .04). On multivariable logistic regression, not completing a screening mammography was associated with having an increasing number of unmet social needs (OR, 0.74; 95% CI, 0.55-0.99; P = .047) and an increasing age at diagnosis (OR, 0.92; 95% CI, 0.89-0.96; P < .001). Moreover, increasing unmet social needs was significantly associated with late-stage diagnosis above and beyond screening mammography (OR, 1.38; 95% CI, 1.01-1.89; P = .04). Conclusions and Relevance: In this cohort study, access to screening mammography did not translate to utilization of screening mammography, increasing unmet social needs were significantly associated with lower rates of screening mammography, and those with increasing unmet social needs were more likely to present with late-stage disease. This association transcended recruitment site (SNH vs ACC), indicating that patients in either hospital setting may benefit from unmet social needs screening to overcome access to care barriers associated with late-stage disease at diagnosis.

Major complications of sigmoid vaginoplasty: a case series.

This case series explores the major complications following sigmoid vaginoplasty in two transgender female patients. Both patients experienced significant post-operative complications, including stenosis and abscess formation, leading to sigmoid conduit ischemia and necrosis. These complications required major surgical interventions and multidisciplinary care, highlighting the complexity of these procedures and their potential morbidity. Our analysis suggests that the initial stenotic insult led to obstruction and vascular insult to the sigmoid conduit, necessitating resection of the affected bowel. The outcomes underscore the need for collaboration across specialties for optimal post-operative monitoring and management. This study advocates for future management guidelines promoting multidisciplinary collaboration to reduce morbidity and resource burdens associated with complications. Despite the complications, sigmoid vaginoplasty remains a viable gender affirmation surgery, providing an effective analogue to vaginal mucosa and offering improved neovaginal depth.

Examination Scores but not Clinical Performance Correlate With Duration of Preclinical Didactic Time: A Synchronous Comparison of Second- Versus Third-Year Medical Students on the Surgery Clerkship.

OBJECTIVE: Numerous institutions have reduced preclinical didactic time to facilitate earlier clinical exposure during the second year of medical education. However, the effects that shortened preclinical education may have on performance in the surgery clerkship are unclear. This study aims to compare the clinical and examination performance of second- (MS2) and third-year (MS3) students synchronously completing an identical surgery clerkship. DESIGN: All students completing the surgery clerkship (identical didactics, examinations, clinical rotations, etc.) were included. MS3s received 24 months of preclinical education, whereas MS2s received 14 months. Performance outcomes included weekly quizzes based on lectures, NBME Surgery Shelf Exam, numeric clinical evaluations, objective structured clinical examination (OSCE) scores, and overall clerkship grades. SETTING: University of Miami Miller School of Medicine. PARTICIPANTS: All second- (MS2) and third-year (MS3) medical students completing the Surgery Clerkship over 1 year (n = 395). RESULTS: There were 199 MS3 (50%) and 196 MS2 (50%) students. MS3s demonstrated higher median shelf exams (77% vs 72% MS2s), weekly quiz score averages (87% vs 80% MS2s), clinical evaluations (96% vs 95% MS2s), and overall clerkship grades (89% vs 87% MS2s), all p < 0.020. There was no difference in median OSCE performance (both 92%; p = 0.499). A greater proportion of MS3 students performed in the highest 50% of weekly quiz scores (57% vs 43% MS2), NBME shelf exams (59% vs 39% MS2), and overall clerkship grades (45% vs 37% MS2), all p < 0.010. No significant difference in the proportion of students placing in the top 50% of clinical parameters including the OSCE (48% MS3 vs 46% MS2; p = 0.106) and clinical evaluations (45% MS3 vs 38%; p = 0.185) was observed. CONCLUSIONS: Although the duration of preclerkship education may correspond to examination scores, MS2s and MS3s perform similarly on clinical metrics. Future strategies to enhance available preclinical didactic time and preparation for examinations are needed.

Nationwide Outcomes of Pancreaticoduodenectomy for Pancreatic Malignancies: Center Volume Matters.

BACKGROUND: Complex surgeries such as pancreaticoduodenectomies (PD) have been shown to have better outcomes when performed at high-volume centers (HVCs) compared to low-volume centers (LVCs). Few studies have compared these factors on a national level. The purpose of this study was to analyze nationwide outcomes for patients undergoing PD across hospital centers with different surgical volumes. METHODS: The Nationwide Readmissions Database (2010-2014) was queried for all patients who underwent open PD for pancreatic carcinoma. High-volume centers were defined as hospitals where 20 or more PDs were performed per year. Sociodemographic factors, readmission rates, and perioperative outcomes were compared before and after propensity score-matched analysis (PSMA) for 76 covariates including demographics, hospital factors, comorbidities, and additional diagnoses. Results were weighted for national estimates. RESULTS: A total of 19,810 patients were identified with age 66 ± 11 years. There were 6,840 (35%) cases performed at LVCs, and 12,970 (65%) at HVCs. Patient comorbidities were greater in the LVC cohort, and more PDs were performed at teaching hospitals in the HVC cohort. These discrepancies were controlled for with PSMA. Length of stay (LOS), mortality, invasive procedures, and perioperative complications were greater in LVCs when compared to HVCs before and after PSMA. Additionally, readmission rates at one year (38% vs 34%, P < .001) and readmission complications were greater in the LVC cohort. CONCLUSIONS: Pancreaticoduodenectomy is more commonly performed at HVCs, which is associated with less complications and improved outcomes compared to LVCs.